The shapes of neuronal arborization have a fundamental role in the organization and circuitry of the nervous system. Modifications to neuronal form have been produced experimentally by a number of environmental insults such as malnutrition, x-irradiation and viruses, or by genetically controlled breeding of mice. Such alterations provide a means of defining substructural determinants of neuronal shape as well as clues to the factors which control the formation of developing cell projections. By comparing neuronal shape parameters with 3-dimensional quantitative aspects of subcellular structure between control and experimental animals, it will be possible to determine which underlying parameters change in accordance with neuronal shape. Using computerized, 3-dimensional, reconstruction techniques, dendritic trees of neurons will be analyzed for several fundamental parameters of shape, as well as the overall parameters of arborization. The subcellular components of neurons, microtubules, neurofilaments and endoplasmic reticulum will be quantitated for density and arrangement. A rat model of malnutrition will be used to produce changes in Purkinje cells of the cerebellum and in pyramidal cells of the frontal cortex. The mutant weaver mouse will be studied in conjunction with the malnutrition model to determine if the effects are similar in a model of cerebellar neuropil reduction which has developed under normal nourishment. Correlation of these parameters in normal and experimentally malnourished groups is expected to demonstrate the effects which a deficiency in nutrition during crucial developmental periods has on subcellular structures and on the shape of mature neurons. Through these fundamental principles we expect to better understand how cell forms develop and how circuitry modifications evolve.